Effects of Proteoglycans on Oxidative/Nitrative Stress

Abstract

Objective: Enhanced production of reactive oxygen and/or nitrogen species in biological tissues leads to oxidative and nitrative stress, a general pathophysiological phenomenon playing a role in the development of various human diseases including cardiovascular and neurological disorders. Method: Reactive oxygen and/or nitrogen species interact with lipids, DNA and proteins via oxidative or radical- mediated reactions, potentially leading to cell damage or death. Proteoglycans are among the most important structural and functional macromolecules in most tissues. The chemical structure of these molecules consist of a core protein onto which one or more negatively charged glycosaminoglycan (GAG) chain(s) are covalently attached. Interaction of proteoglycans with oxidative/nitrative stress has been demonstrated in various experimental systems. In this review, we discuss the modulatory effects of proteoglycans on tissue oxidative/ nitrative stress and consequent cellular function especially in cardiovascular and neurological disorders. Conclusion: Proteoglycans have been implicated in both deleterious and potentially cytoprotective mechanisms. The protective mechanisms include chelation of positively charged transitional metal ions (e.g. iron and copper), scavenging superoxide anions by extracellular superoxide dismutase, building pericellular net and mediation of signal transduction pathways. Although these results may implicate proteoglycans as potential therapeutic targets, more research should be done to better explore proteoglycans as modulators of reactive oxygen/nitrogen species and to determine their possible therapeutic value in disorders accompanied by oxidative/ nitrative stress. Keywords: Proteoglycan, mucopolysaccharide, GAG, ROS, EC-SOD, perineural net, chelation, superoxide, nitric oxide, peroxynitrite.